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14 "Keon Uk Park"
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Lung and Thoracic cancer
Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
Ki Hyeong Lee, Byoung Chul Cho, Myung-Ju Ahn, Yun-Gyoo Lee, Youngjoo Lee, Jong-Seok Lee, Joo-Hang Kim, Young Joo Min, Gyeong-Won Lee, Sung Sook Lee, Kyung-Hee Lee, Yoon Ho Ko, Byoung Yong Shim, Sang-We Kim, Sang Won Shin, Jin-Hyuk Choi, Dong-Wan Kim, Eun Kyung Cho, Keon Uk Park, Jin-Soo Kim, Sang Hoon Chun, Jangyoung Wang, SeokYoung Choi, Jin Hyoung Kang
Cancer Res Treat. 2024;56(1):48-60.   Published online June 27, 2023
DOI: https://doi.org/10.4143/crt.2023.453
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Citations

Citations to this article as recorded by  
  • First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis
    Jietao Ma, Xiaoxue Pang, Shuling Zhang, Letian Huang, Li Sun, Chengbo Han
    Scientific Reports.2024;[Epub]     CrossRef
  • 6,132 View
  • 578 Download
  • 3 Web of Science
  • 1 Crossref
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Head and Neck cancer
Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01)
Yun-Gyoo Lee, Eun Joo Kang, Bhumsuk Keam, Jin-Hyuk Choi, Jin-Soo Kim, Keon Uk Park, Kyoung Eun Lee, Hyo Jung Kim, Keun-Wook Lee, Min Kyoung Kim, Hee Kyung Ahn, Seong Hoon Shin, Hye Ryun Kim, Sung-Bae Kim, Hwan Jung Yun
Cancer Res Treat. 2022;54(1):109-117.   Published online April 27, 2021
DOI: https://doi.org/10.4143/crt.2020.1329
AbstractAbstract PDFPubReaderePub
Purpose
Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods
Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results
Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion
Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.

Citations

Citations to this article as recorded by  
  • Circulating tumor DNA determines induction chemotherapy response in HPV associated oropharyngeal squamous cell carcinoma: A pilot study
    Zachary M. Huttinger, Emile Gogineni, Sujith Baliga, Dukagjin M. Blakaj, Priyanka Bhateja, Marcelo Bonomi, Stephen Y. Kang, Matthew O. Old, Nolan B. Seim, Kyle K. VanKoevering, Amit Agrawal, Enver Ozer, James W. Rocco, Catherine T. Haring
    Oral Oncology.2025; 161: 107179.     CrossRef
  • Clinical decision pathway and management of locally advanced head and neck squamous cell carcinoma: A multidisciplinary consensus in Asia-Pacific
    Ye Guo, Torahiko Nakashima, Byoung Chul Cho, Darren W.-T. Lim, Muh-Hwa Yang, Pei-Jen Lou, June Corry, Jin Ching Lin, Guo Pei Zhu, Kyung Hwan Kim, Bin Zhang, Zhiming Li, Ruey-Long Hong, Junice Yi Siu Ng, Ee Min Tan, Yan Ping Liu, Con Stylianou, Carmel Spit
    Oral Oncology.2024; 148: 106657.     CrossRef
  • Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for locally advanced head and neck squamous cell carcinoma
    Ping Han, Faya Liang, Pan Song, Taowei Wu, Yangyang Li, Ming Gao, Peiliang Lin, Jianming Fan, Xiaoming Huang
    Holistic Integrative Oncology.2024;[Epub]     CrossRef
  • Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience
    Hyun Bang, Hyeon-Jong Kim, Seung Lee, Hyun Shim, Jun Hwang, Woo Bae, Ik-Joo Chung, Sang-Hee Cho
    Oncology Letters.2024;[Epub]     CrossRef
  • Role of induction chemotherapy in advanced‐stage olfactory neuroblastoma
    Sung‐Woo Cho, Bhumsuk Keam, Keun‐Wook Lee, Ji‐Won Kim, Doo Hee Han, Hyun Jik Kim, Jeong‐Whun Kim, Dong‐Young Kim, Chae‐Seo Rhee, Yun Jung Bae, Ji‐Hoon Kim, Keun‐Yong Eom, Hong‐Gyun Wu, Yong Hwy Kim, Chae‐Yong Kim, Sun Ha Paek, Hyojin Kim, Tae‐Bin Won
    International Forum of Allergy & Rhinology.2024; 14(12): 1882.     CrossRef
  • Intra-Arterial Chemotherapy for Locally Advanced Oral Cavity Cancer
    B. B. Vyzhigina, M. A. Kropotov, B. I. Dolgushin, D. A. Safarov, I. V. Pogrebnyakov, S. B. Alieva
    Journal of oncology: diagnostic radiology and radiotherapy.2024; 7(3): 62.     CrossRef
  • Response to induction chemotherapy as a prognostic indicator in locally advanced head and neck squamous cell carcinoma
    Francesca Huwyler, Roland Giger, Ruben Bill, Daniel Rauch, Simon Haefliger
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Response to induction chemotherapy in sinonasal malignancies: A single‐institutional experience
    Sarah C. Nyirjesy, Rachel Fenberg, Margaret A. Heller, Ryan T. Judd, Michael M. Li, Brandon Koch, Marcelo Bonomi, Ricardo L. Carrau, Kyle K. VanKoevering
    Head & Neck.2023; 45(6): 1445.     CrossRef
  • Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives
    Michaela Svajdova, Pavol Dubinsky, Tomas Kazda, Branislav Jeremic
    Cancers.2022; 14(21): 5385.     CrossRef
  • 7,218 View
  • 231 Download
  • 7 Web of Science
  • 9 Crossref
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Head and Neck Cancer
Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12
Yun-Gyoo Lee, Hyun Chang, Bhumsuk Keam, Sang Hoon Chun, Jihyun Park, Keon Uk Park, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, Keun-Wook Lee, Hye Ryun Kim, Sung-Bae Kim, Myung-Ju Ahn, In Gyu Hwang
Cancer Res Treat. 2021;53(3):671-677.   Published online December 7, 2020
DOI: https://doi.org/10.4143/crt.2020.824
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.

Citations

Citations to this article as recorded by  
  • Neutrophil‐to‐Lymphocyte Ratio and Pembrolizumab Outcomes in Oral Cavity Squamous Cell Carcinoma
    Angeline A. Truong, Rex H. Lee, Xin Wu, Alain P. Algazi, Hyunseok Kang, Ivan H. El‐Sayed, Jonathan R. George, Chase M. Heaton, William R. Ryan, Yena Jeon, Mi‐Ok Kim, Patrick K. Ha, Katherine C. Wai
    Otolaryngology–Head and Neck Surgery.2025; 172(2): 548.     CrossRef
  • Risk Factors for Progressive Disease After Immune Checkpoint Inhibitor Therapy in Head and Neck Squamous Cell Carcinoma
    Seo Yoon Jang, Yun‐Gyoo Lee, Sang Hoon Chun, Ji Hyun Park, Keon Uk Park, Hyun Chang, Keun‐Wook Lee, Hye Ryun Kim, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, In Gyu Hwang, Myung‐Ju Ahn, Sung‐Bae Kim, Bhumsuk Keam
    Head & Neck.2025;[Epub]     CrossRef
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    Jialin Su, Yuning Li, Shuhua Tan, Tianli Cheng, Yongzhong Luo, Lemeng Zhang
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  • Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study
    Dong Hyun Kim, Seung Taek Lim, Hye Ryun Kim, Eun Joo Kang, Hee Kyung Ahn, Yun-Gyoo Lee, Der Sheng Sun, Jung Hye Kwon, Sang-Cheol Lee, Hyun Woo Lee, Min Kyoung Kim, Bhumsuk Keam, Keon-Uk Park, Seong-Hoon Shin, Hwan Jung Yun
    Oral Oncology.2024; 151: 106739.     CrossRef
  • Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature
    Lei Liu, Qiang Liu
    Scientific Reports.2024;[Epub]     CrossRef
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    Quan Wang, Xiangzhi Yin, Shengxia Wang, Haijun Lu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Predictive value of early dynamic changes of NLR and PLR for the efficacy of immune checkpoint inhibitor in head and neck squamous cell carcinoma
    Dong Hyun Kim, Seo Yoon Jang, Bhumsuk Keam
    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2024; 138(6): 763.     CrossRef
  • Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma
    Piero Giuseppe Meliante, Federica Zoccali, Marco de Vincentiis, Massimo Ralli, Carla Petrella, Marco Fiore, Antonio Minni, Christian Barbato
    Diagnostics.2023; 13(5): 862.     CrossRef
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    Catherine T. Haring, Lulia A. Kana, Sarah M. Dermody, Collin Brummel, Jonathan B. McHugh, Keith A. Casper, Steven B. Chinn, Kelly M. Malloy, Michelle Mierzwa, Mark E. P. Prince, Andrew J. Rosko, Jennifer Shah, Chaz L. Stucken, Andrew G. Shuman, J. Chad Br
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  • Immunotherapy with PD-1 Inhibitor Nivolumab in Recurrent/Metastatic Platinum Refractory Head and Neck Cancers—Early Experiences from Romania and Literature Review
    Camil Ciprian Mireștean, Mihai Cosmin Stan, Michael Schenker, Constantin Volovăț, Simona Ruxandra Volovăț, Dragoș Teodor Petru Iancu, Roxana Irina Iancu, Florinel Bădulescu
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    Sagar Dholariya, Ragini D. Singh, Amit Sonagra, Dharamveer Yadav, Bhairavi N. Vajaria, Deepak Parchwani
    Critical Reviews™ in Oncogenesis.2023; 28(2): 11.     CrossRef
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    Frontiers in Oncology.2023;[Epub]     CrossRef
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    Maria A. Lopez-Olivo, Valeria Valerio, Aliza R. Karpes Matusevich, Marianela Brizio, Michelle Kwok, Yimin Geng, Maria E. Suarez-Almazor, Ines Colmegna
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    Xing-xing Huo, Shu-jie Wang, Hang Song, Ming-de Li, Hua Yu, Meng Wang, Hong-xiao Gong, Xiao-ting Qiu, Yong-fu Zhu, Jian-ye Zhang
    Frontiers in Pharmacology.2021;[Epub]     CrossRef
  • 7,403 View
  • 227 Download
  • 18 Web of Science
  • 19 Crossref
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Lung cancer
Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea
Sun Min Lim, Sang-We Kim, Byoung Chul Cho, Jin Hyung Kang, Myung-Ju Ahn, Dong-Wan Kim, Young-Chul Kim, Jin Soo Lee, Jong-Seok Lee, Sung Yong Lee, Keon Uk Park, Ho Jung An, Eun Kyung Cho, Tae Won Jang, Bong-Seog Kim, Joo-Hang Kim, Sung Sook Lee, Im-II Na, Seung Soo Yoo, Ki Hyeong Lee
Cancer Res Treat. 2020;52(4):1112-1119.   Published online May 15, 2020
DOI: https://doi.org/10.4143/crt.2020.245
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.
Materials and Methods
Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.
Results
Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.
Conclusion
This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Citations

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    Ana Ortega-Franco, Clare Hodgson, Haseem Raja, Mathew Carter, Colin Lindsay, Sarah Hughes, Laura Cove-Smith, Paul Taylor, Yvonne Summers, Fiona Blackhall, Raffaele Califano
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    Frontiers in Oncology.2021;[Epub]     CrossRef
  • 10,615 View
  • 308 Download
  • 15 Web of Science
  • 9 Crossref
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Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting
Jin Hyoung Kang, Jung Hye Kwon, Yun-Gyoo Lee, Keon Uk Park, Ho Jung An, Joohyuk Sohn, Young Mi Seol, Hyunwoo Lee, Hwan-Jung Yun, Jin Seok Ahn, Ji Hyun Yang, Hunho Song, Dong-Hoe Koo, Jin Young Kim, Gun Min Kim, Hwa Jung Kim
Cancer Res Treat. 2020;52(3):907-916.   Published online March 18, 2020
DOI: https://doi.org/10.4143/crt.2019.713
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting.
Materials and Methods
Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.
Results
A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.
Conclusion
In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Citations

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    Baoxia Fang, Lijun Zhao, Shirong Yu, Fuchao Chen
    Dose-Response.2024;[Epub]     CrossRef
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A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13
Kwai Han Yoo, Su Jin Lee, Jinhyun Cho, Ki Hyeong Lee, Keon Uk Park, Ki Hwan Kim, Eun Kyung Cho, Yoon Hee Choi, Hye Ryun Kim, Hoon-Gu Kim, Heui June Ahn, Ha Yeon Lee, Hwan Jung Yun, Jin-Hyoung Kang, Jaeheon Jeong, Moon Young Choi, Sin-Ho Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):718-726.   Published online September 3, 2018
DOI: https://doi.org/10.4143/crt.2018.324
AbstractAbstract PDFPubReaderePub
Purpose
The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Materials and Methods
We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles.
Results
A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms.
Conclusion
The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma
Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim
Cancer Res Treat. 2019;51(1):300-312.   Published online May 9, 2018
DOI: https://doi.org/10.4143/crt.2018.012
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

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Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer
Miso Kim, Bhumsuk Keam, Tae-Min Kim, Hoon-Gu Kim, Jin-Soo Kim, Sung Sook Lee, Seong Hoon Shin, Min Kyoung Kim, Keon Uk Park, Dong-Wan Kim, Hwan Jung Yun, Jong Seok Lee, Dae Seog Heo
Cancer Res Treat. 2017;49(2):416-422.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.121
AbstractAbstract PDFPubReaderePub
Purpose
The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer.
Materials and Methods
Patients were treated with irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity.
Results
A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the perprotocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%).
Conclusion
Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

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A Phase II Study to Evaluate the Efficacy of Ramosetron, Aprepitant, and Dexamethasone in Preventing Cisplatin-Induced Nausea and Vomiting in Chemotherapy-Naive Cancer Patients
Geundoo Jang, Hun Ho Song, Keon Uk Park, Hyeong Su Kim, Dae Ro Choi, Jung Hye Kwon, Ho Young Kim, Boram Han, Jung Han Kim, Joo Young Jung, Hyo Jung Kim, Dae Young Zang
Cancer Res Treat. 2013;45(3):172-177.   Published online September 30, 2013
DOI: https://doi.org/10.4143/crt.2013.45.3.172
AbstractAbstract PDFPubReaderePub
PURPOSE
Combination therapy with aprepitant, serotonin receptor antagonist, and steroids improves the complete response rate of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, it is not known whether ramosetron is suitable for administration in combination with aprepitant. Therefore, we conducted a multicenter, open-label, prospective, phase II study in order to assess the efficacy and tolerability of combination therapy with ramosetron, aprepitant, and dexamethasone (RAD) for prevention of cisplatin-based CINV in chemotherapy-naive patients with solid cancers.
MATERIALS AND METHODS
Forty-one patients with various solid cancers (31 male and 10 female; median age, 59 years) who received treatment with highly emetogenic chemotherapy (median cisplatin dose, 70 mg/m2; range 50 to 75 mg/m2) were enrolled in this study. Oral aprepitant (125 mg on day 1; 80 mg on days 2 and 3), intravenous ramosetron (0.6 mg on day 1), and oral dexamethasone (12 mg on day 1; 8 mg on days 2-4) were administered for prevention of CINV.
RESULTS
The complete response (no emesisand retching and no rescue medication) rate was 94.9% in the acute period (24 hours post-chemotherapy), 92.3% in the delayed period (24-120 hours post-chemotherapy), and 92.3% in the overall period (0-120 hours). The absolute complete response (complete response plus no nausea) rate was 74.4% in the acute period, 51.3% in the delayed period, and 46.2% in the overall period. There were no grade 3 or 4 toxicities related to these antiemetic combinations.
CONCLUSION
RAD regimen is a safe and effective antiemetic treatment for prevention of CINV in patients receiving highly emetogenic chemotherapy.

Citations

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    Hyo Jung Kim, Sang Won Shin, Eun-Kee Song, Na-Ri Lee, Jun Suk Kim, Jin Seok Ahn, Hwan-Jung Yun, Yo-Han Cho, Keon Uk Park, Si-Young Kim, Joung Soon Jang, Sang-We Kim, Hyun Woo Lee, Se Ryeon Lee, Yang Soo Kim, Soon Nam Lee, Yoon Ho Ko, Hwa Jung Kim, Jin-Hyo
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    Hannah Kenward, Ludovic Pelligand, Jonathan Elliott
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    Erin M. Rock, Cheryl L. Limebeer, Linda A. Parker
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Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement
Byung Woog Kang, Joon Ho Moon, Yee Soo Chae, Soo Jung Lee, Jong Gwang Kim, Yeo-Kyeoung Kim, Je-Jung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Jin Young Kim, Young Rok Do, Keon Uk Park, Hong Suk Song, Ki Young Kwon, Min Kyung Kim, Kyung Hee Lee, Myung Soo Hyun, Hun Mo Ryoo, Sung Hwa Bae, Hwak Kim, Sang Kyun Sohn
Cancer Res Treat. 2013;45(2):112-117.   Published online June 30, 2013
DOI: https://doi.org/10.4143/crt.2013.45.2.112
AbstractAbstract PDFPubReaderePub
PURPOSE
We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.
MATERIALS AND METHODS
A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively.
RESULTS
The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group.
CONCLUSION
BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab.

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Metachronous Double Primary Cancer after Diagnosis of Gastric Cancer
Jin Young Kim, Won Young Jang, Mi Hwa Heo, Kang Kuk Lee, Young Rok Do, Keon Uk Park, Hong Suk Song, Yoon Nyun Kim
Cancer Res Treat. 2012;44(3):173-178.   Published online September 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.3.173
AbstractAbstract PDFPubReaderePub
PURPOSE
The pattern of double primary cancers after treatment for gastric cancer is important for a patient's survival.
MATERIALS AND METHODS
We analyzed the clinicopathologic data of 214 gastric cancer patients from October 1996 to November 2007 with regard to metachronous second primary cancers.
RESULTS
Out of 5,778 patients with gastric cancer, metachronous second primary cancers occurred in 214 patients. The median age was 61.8 years, the number of male and female patients was 140 (65.4%), 74 (34.6%), respectively. The median time to the occurrence of second cancers after diagnosis of the first was 39.2 months (standard deviation, 31.2 months). The most common cancer was colorectal cancer, which occurred in 44 patients (20.6%), and lung cancer in 33 patients (15.4%), hepatocellular carcinoma in 26 patients (12.1%), ovarian cancer in 15 patients (7.0%), cervical cancer in 12 patients (7.0%), breast cancer in 11 patients (5.1%), and esophageal cancer in 11 patients (5.1%). The observed/expected (O/E) ratio showed a significant increase in colorectal (1.25), male biliary (1.60), ovarian (8.72), and cervical cancer (3.33) with primary gastric cancer. After five years from diagnosis of gastric cancer, secondary cancer occurred in 50 patients (23.4%), and breast cancer, prostate cancer, laryngeal cancer, lung cancer, and hepatocellular carcinoma were the most frequent.
CONCLUSION
The O/E ratio showed a significant increase in colorectal, male biliary, ovarian, and cervical cancer with primary gastric cancer, and second primary cancer as the main cause of death for these patients. A follow-up examination for metachronous double primary cancer is needed in order to improve the survival time in patients with gastric cancer.

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    Makiko So, Aya Shimoji, Yoko Iemura, Ai Suizu, Shuichiro Iwami, Masahito Hoki, Shinsuke Shibuya
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    Ali Hemade, Souheil Hallit
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    Yi-Jia Lin, Hua-Xian Chen, Feng-Xiang Zhang, Xian-Sheng Hu, Hai-Juan Huang, Jian-Hua Lu, Ye-Zi Cheng, Jun-Sheng Peng, Lei Lian
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    Jeong Youp Park
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    Alex Emmanuel Elobu, Ashok Thorat, Vianney Kweyamba, Rakesh Rai
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A Multi-Center, Phase II Clinical Trial of Padexol™ (Paclitaxel) and Cisplatin for Patients Suffering with Advanced Gastric Cancer
Min Kyoung Kim, Kyung Hee Lee, Myung Soo Hyun, Young Rok Do, Hong Suk Song, Won Sik Lee, Keon Uk Park, Jin Ho Baek, Jong Gwang Kim
Cancer Res Treat. 2005;37(6):349-353.   Published online December 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.6.349
AbstractAbstract PDFPubReaderePub
Purpose

We conducted a multi-center, phase II trial to evaluate the efficacy and safety of using Padexol (a paclitaxel formulation) combined with cisplatin for the patients suffering with advanced gastric adenocarcinoma.

Materials and Methods

39 patients (median age: 60 years; males: 90%) who were diagnosed with advanced gastric cancer were enrolled from 5 hospitals. Padexol 175 mg/m2 was administered as a 3-hr infusion, and this was followed by cisplatin 75 mg/m2 as an intravenous infusion on day 1, once every 3 weeks.

Results

Out of these 39 patients, 34 patients were assessable for treatment efficacy and 39 patients were assessable for the toxicity. Objective responses occurred in 13 patients (33%); 1 patient (3%) had a complete response and 12 patients (31%) had partial responses. 6 patients (15%) achieved a stable disease state. The median duration of response was 7.1 months, and the median time to progression and the overall survival were 4.8 months and 6.7 months, respectively. The major treatment-related adverse events were hematologic toxicity, including WHO grade 3 or 4 neutropenia in 13 patients (33%). However, febrile neutropenia occurred in only 1 patient and the non-hematologic toxicity was usually mild.

Conclusion

The combination of Padexol and cisplatin was found to be active and it seems to be a relatively well-tolerated regimen for the treatment of advanced gastric cancer.

Citations

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  • Effect of the Weekly Administration of Liposome–Paclitaxel Combined with S-1 on Advanced Gastric Cancer
    Lei Chen, Qiang Chen, Zhixiang Zhuang, Yusong Zhang, Jialong Tao, Liqin Shen, Xudong Shen, Zhigang Chen, Ji Wang, Minggao Zhu, Hui Wang
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    Yuji Ueda, Hisakazu Yamagishi, Daisuke Ichikawa, Kazuma Okamoto, Eigo Otsuji, Jun Morii, Kinya Koizumi, Naoki Kakihara, Masataka Shimotsuma, Tetsuro Yamashita, Fumihiro Taniguchi, Hideki Aragane, Hiroshi Nishi, Yoshiki Itokawa, Satoshi Morita, Junichi Sak
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    Q. Sun, C. Liu, H. Zhong, B. Zhong, H. Xu, W. Shen, D. Wang
    Japanese Journal of Clinical Oncology.2009; 39(4): 237.     CrossRef
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    Bong-Gun Seo, Sung Yong Oh, Dong Mee Lee, Hyun Seung Yoo, Suee Lee, Seong-Geun Kim, Sung-Hyun Kim, Hyuk-Chan Kwon, Hyo-Jin Kim
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  • Multicenter phase II study of weekly paclitaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer
    Jong Gwang Kim, Sang Kyun Sohn, Hong Suk Song, Ki-Young Kwon, Young Rok Do, Kyung Hee Lee, Myung Soo Hyun, Hun Mo Ryoo, Sung Hwa Bae, Keon Uk Park, Jin Ho Baek, Won Sik Lee, Joo Seop Chung, Goon Jae Cho, Chang-Hak Sohn, Jung Soon Jang, Ho Young Chung, Wan
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    Hoon-Kyo Kim, Jun Suk Kim, Hun Mo Ryoo, Dong Gun Shin, Byoung Young Shim, Kyong Hwa Park, Sung Hwa Bae, Chi Hong Kim
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The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia
Young Joo Min, Cheol Won Suh, Keon Uk Park, Sung Soo Yoon, Chan Hyung Park, Hong Ghi Lee
Cancer Res Treat. 2003;35(1):66-68.   Published online February 28, 2003
DOI: https://doi.org/10.4143/crt.2003.35.1.66
AbstractAbstract PDF
PURPOSE
This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.
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Case Report
A Case of a Young Woman with Hepatosplenic gamadelta T-cell Lymphoma
Il Gwon Park, Cheol Won Suh, Joo Ryung Hur, Sun Jong Kim, Keon Uk Park, Seong Je Park, Don Dae Seo, Man Su Ahn, Geun Doo Jang, Woo Kun Kim
Cancer Res Treat. 2001;33(3):264-268.   Published online June 30, 2001
DOI: https://doi.org/10.4143/crt.2001.33.3.264
AbstractAbstract PDF
Most T-cell lymphomas arise from mature alpabeta T-cells and commonly involve the nodes. Lymphomas bearing the gamadelta T-cell receptor (TCR) are very rare, and involve the lymph nodes minimally, if at all. Hepatosplenic gamadelta T-cell lymphoma is a recently identified, rare entity in which lymphoma cells bearing the gamadelta TCR infiltrate the sinusoids of the liver, splenic red pulp, and bone marrow. Its leukemic transformation is even more rare. Recently, we experienced a case of hepatosplenic gamadelta T-cell lymphoma in a 19-year-old woman who presented with epigastric pain, fever, massive splenomegaly, andpancytopenia. The splenectomy specimen and excisional biopsy of the liver revealed the infiltration of atypical T lymphocytes with the immunophenotypic markers of CD3 (+), CD45RO (pan-T antigen) (+), TIA-1(+), CD4(-),CD8 (-), CD56 (-), and S100 (-) in the sinusoids of the liver and splenic red pulp. Polymerase chain reaction (PCR) showed that these cells had the expression of the TCR gama gene rearrangements. Though the pancytopenia had improved after the splenectomy, the response of chemotherapy was transient. Her disease progressed rapidly and she expired in the leukemic phase. We report a case of hepatosplenic gamadelta T-cell lymphoma that developed in a young woman, along with a brief review of the literature.

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